The role of specific neurotransmitters in regulating neuronal activity in the basal ganglia and related areas has been investigated in order to develop a basis for designing improved pharmacological treatments for neurological disorders involving these brain regions. Current topics under investigation are: 1) Modulation of substania nigra (SN) dopamine cell activity. Although dopamine and SN pars reticulata neurons possess at least two types of specific excitatory amino acid receptors, excitatory amino acid antagonists do not block spontaneous discharge of these cells. The neuropeptide, substance K, which shares a precursor molecule with the excitatory peptide, substance P, appears present in striatonigral neurons but, like substance P, exerts an excitatory effect on only a subpopulation of reticulata neurons, located in the region where substance K receptors have been demonstrated. Thus, known excitatory inputs to the SN do not appear to contribute to the tonic activity of the dopamine neurons. 2) Stimulation of dopamine receptors subtypes. To better understand which dopamine receptors play the most significant roles in determining the effects of dopamine agonist administration, the effects of stimulating different subtypes of dopamine receptors have been examined. D-2 dopamine receptor-mediated processes exert different effects on the tonic activity of cells in the globus pallidus as compared with the SN pars reticulata. They also differentially affect subpopulations within these two regions in a manner dependent upon the state of sensitivity of the dopamine receptors. Blockade of D-1 receptors does not affect the actions of D-2 agonists on the SN pars compacta dopamine neurons, nor does stimulation of D-1 receptors affect tonic dopamine cell activity. However, blockade of D-1 receptors does appear to markedly attenuate the D-2 mediated effects of dopamine agonists on neuronal activity in the globus pallidus. These results suggest heretofore unappreciated but potentially significant interactions between striatal D-1 and D-2 receptors may be involved in regulating basal ganglia output.